NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia

 

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dc.contributor.author Cnops, Jennifer en_ZA
dc.contributor.author Trez, Carl De en_ZA
dc.contributor.author Stijlemans, Benoit en_ZA
dc.contributor.author Keirsse, Jiri en_ZA
dc.contributor.author Kauffmann, Florence en_ZA
dc.contributor.author Barkhuizen, Mark en_ZA
dc.contributor.author Keeton, Roanne en_ZA
dc.contributor.author Boon, Louis en_ZA
dc.contributor.author Brombacher, Frank en_ZA
dc.contributor.author Magez, Stefan en_ZA
dc.date.accessioned 2015-12-28T06:51:16Z
dc.date.available 2015-12-28T06:51:16Z
dc.date.issued 2015 en_ZA
dc.identifier.citation Cnops, J., De Trez, C., Stijlemans, B., Keirsse, J., Kauffmann, F., Barkhuizen, M., ... & Magez, S. (2015). NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. PLoS pathogens, 11(6). doi:10.1371/journal.ppat.1004964 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16065
dc.identifier.uri http://dx.doi.org/10.1371/journal.ppat.1004964
dc.description.abstract African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open access article distributed under the terms of the <a href= en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plospathogens en_ZA
dc.subject.other Anemia en_ZA
dc.subject.other Cytotoxic T cells en_ZA
dc.subject.other Spleen en_ZA
dc.subject.other Macrophages en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Bone marrow cells en_ZA
dc.subject.other Cloning en_ZA
dc.subject.other Inflammation en_ZA
dc.title NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2015 Cnops et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Cnops, J., Trez, C. D., Stijlemans, B., Keirsse, J., Kauffmann, F., Barkhuizen, M., ... Magez, S. (2015). NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. <i>PLoS One</i>, http://hdl.handle.net/11427/16065 en_ZA
dc.identifier.chicagocitation Cnops, Jennifer, Carl De Trez, Benoit Stijlemans, Jiri Keirsse, Florence Kauffmann, Mark Barkhuizen, Roanne Keeton, Louis Boon, Frank Brombacher, and Stefan Magez "NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16065 en_ZA
dc.identifier.vancouvercitation Cnops J, Trez CD, Stijlemans B, Keirsse J, Kauffmann F, Barkhuizen M, et al. NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. PLoS One. 2015; http://hdl.handle.net/11427/16065. en_ZA
dc.identifier.ris TY - Journal Article AU - Cnops, Jennifer AU - Trez, Carl De AU - Stijlemans, Benoit AU - Keirsse, Jiri AU - Kauffmann, Florence AU - Barkhuizen, Mark AU - Keeton, Roanne AU - Boon, Louis AU - Brombacher, Frank AU - Magez, Stefan AB - African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia. DA - 2015 DB - OpenUCT DO - 10.1371/journal.ppat.1004964 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia TI - NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia UR - http://hdl.handle.net/11427/16065 ER - en_ZA


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